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| United States Patent |
5,696,105
|
|
Hackler
|
December 9, 1997
|
Antifungal nail composition
Abstract
The invention relates to a composition treating nail fungus or
onychomycosis, which composition includes an effective amount of
mometasone furoate and wherein said composition is topically applied to
the nail that is to be treated for fungus.
| Inventors:
|
Hackler; Walter A. (1616 Sea Bell Circle, Corona del Mar, CA 92625)
|
| Appl. No.:
|
615420 |
| Filed:
|
March 14, 1996 |
| Current U.S. Class: |
514/172 |
| Intern'l Class: |
C07D 031/58 |
| Field of Search: |
514/172
|
References Cited
U.S. Patent Documents
| 4472393 | Sep., 1984 | Shapiro | 424/243.
|
| 4755529 | Jul., 1988 | Higa et al. | 514/468.
|
| 4775529 | Oct., 1988 | Segueira et al. | 424/81.
|
| 4808610 | Feb., 1989 | Munayyer et al. | 514/172.
|
| 5346692 | Sep., 1994 | Wohlrab et al. | 424/61.
|
| 5391367 | Feb., 1995 | DaVincentis et al. | 424/61.
|
| 5420114 | May., 1995 | Clodman et al. | 514/23.
|
| 5422361 | Jun., 1995 | Munayyer et al. | 514/408.
|
| 5422366 | Jun., 1995 | Mintzis et al. | 514/474.
|
| 5464610 | Nov., 1995 | Hayes, Jr. et al. | 424/61.
|
Primary Examiner: Cook; Rebecca
Attorney, Agent or Firm: Hackler; Walter A.
Claims
What is claimed is:
1. A method of treating fungal infection or onychomycosis of the nails in a
patient in need thereof by topically applying a composition consisting
essentially of an effective amount of a 3,20-dioxo-1, 4-pregnadiene
wherein said 3,20-dioxo-1, 4-pregnadiene is mometasone furoate in a
pharmaceutically acceptable vehicle.
2. The method of claim 1 wherein said composition consists essentially of
from 0.01 to 1.0%, by weight, mometasone furoate.
3. The method of claim 2 wherein said composition is a lotion.
4. The method of claim 3 wherein said pharmaceutically-acceptable vehicle
is a hydro-alcoholic base comprising 15 to 50% by weight of propylene
glycol; 20 to 40% by weight of isopropyl alcohol; 20 to 60% by weight
water; 0.1 to 3.0% by weight of a thickening agent, and sufficient buffer
to maintain the pH of the composition within the range of 3.0 to 6.0.
5. The method of claim 2 wherein said composition consists essentially of:
______________________________________
Ingredients Concentration mg/g
______________________________________
Mometasone furoate 1.0
Alcohol Isopropyl USP 400.0
Propylene Glycol USP 300.0
Hydroxypropyl Cellulose 1.5
(Klucel HF)
Sodium Phosphate Monobasic
2.0
Monohydrate R
Phosphoric Acid NF (To adjust
the pH to 4.5 .+-. 0.1.)
Water Purified USP q.s. to make
1 g
______________________________________
6. The method of claim 4 wherein the thickening agent is an acrylic acid
polymer.
7. The method of claim 4 wherein the thickening agent is hydroxypropyl
cellulose.
8. The method of claim 2 wherein said composition is a cream.
9. The method of claim 8 wherein said composition consists essentially of:
0.01 to 0.25% Mometasone Furoate
5 to 20% hexylene glycol
1.0 to 5.0% water
2.0 to 10.0% white wax
4 to 12% of a lipophilic emulsifier having a HLB below 5
0.7 to 4% of a hydrophilic emulsifier having a HLB above 11
0.2 to 2.0% Titanium dioxide
5 to 20% aluminum starch octenylsuccinate
40 to 70% white petrolatum
sufficient acid to adjust the pH of the water to pH 2.5+0.2.
10. The method of claim 9 wherein said composition consists essentially of:
0.05 to 0.15% Mometasone Furoate
9 to 15% hexylene glycol
2 to 4% water purified
4 to 6% white wax
6 to 10% of a lipophilic emulsifier having a HLB below 5
1.2 to 2.5% of a hydrophilic emulsifier having a HLB above 11
0.75 to 1.25% Titanium dioxide
8 to 12% aluminum starch octenylsuccinate
50 to 60% white petrolatum
sufficient acid to adjust the pH of the water to pH 2.5.+-.0.2.
11. The method of claim 8 wherein the acid utilized to adjust the pH of the
water is selected from the group consisting of phosphoric acid,
hydrochloric acid and acetic acid.
12. The method of claim 8 wherein the lipophilic emulsifier is selected
from the group consisting of propylene glycol stearate, ethylene glycol
monolaurate, ethylene glycol monostearate, propylene glycol monolaurate,
and glyceryl monoricinolate.
13. The method of claim 12 wherein the hydrophilic emulsifier is stearyl
alcohol and ceteareth-20, polyethylene glycol monolaurate, polyethylene
glycol distearate, P.O.E. cetyl alcohol, P.O.E. sorbitan monostearate or
P.O.E. sorbitan monooleate.
14. The method of claim 8 wherein said composition consists essentially of
(in mg/g):
Mometasone Furoate 1.0
Hexylene Glycol NF 120.0
Water Purified USP 30.0
White Wax NF 50.0
Propylene Glycol Stearate 80.0
Stearyl Alcohol and Ceteareth-20 70.0 (Promulgen-G)
Titanium Dioxide USP 10.0
Aluminum Starch Octenylsuccinate 100.0
White Petrolatum USP 539.0
Sufficient Phosphoric Acid NF to adjust the pH of the water to pH
2.5.+-.0.2.
15. A method of making unguis inhospitable to the growth of fungal
infection in a patient in need thereof by applying a composition
consisting essentially of an effective amount of mometasone furoate in a
pharmaceutically-acceptable vehicle to the unguis.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a composition treating nail fungus or
onychomycosis, which composition includes mometasone furoate wherein said
composition is topically applied to the nail that is to be treated for
fungus.
2. Description of the Art
Onychomycosis is a disease of the nails (unguis) of the fingers and toes
caused by Epidermophyton floccusum, by several species of Trichophyton or
by Candida albicans. The nails become opaque, white, thickened, fragile
and brittle. It is acknowledged that the therapy of onychomycosis is
difficult and protracted. Oral therapy with antimycotics requires months
of administration, has only a 50% success rate, and must be closely
monitored for side effects.
Unfortunately, such fungal nail infections have proven to be very resistant
to treatment. Systemic administration of anti-fungal drugs is hindered by
limited blood circulation in the nail bed and poor transport to the nail
plate, requiring high dosage levels for long periods of time. Such high
drug dosages can have adverse side effects, and it has been found that
clearance of the infection is often only temporary. Thus, systemic
treatment must often be continued indefinitely.
Topical administration of anti-fungal drugs also suffers certain
limitations. The nail plate is a relatively thick structure which inhibits
penetration of the drug being applied. Moreover, the topical application
of creams, lotions, gels, and the like, is often lost or dissipated in
relatively short times. Although attempts have been made to incorporate
such topically active anti-fungal drugs into film-forming compositions,
e.g., nail polishes or lacquers, to improve drug persistence, such
approaches have not proved entirely satisfactory.
Topical use of generally suitable preparations is ineffective, because of
inadequate penetration through the nail keratin. A proposal of drilling
small holes in the nail to afford the fungicide access to the layers below
has been suggested.
Other local measures, mechanical ablation of affected nail areas, is used
in practice. Extraction of the nail, particularly where multiple nails are
affected, is used but frequently, that is not an acceptable option from
the standpoint of the patient.
Moreover, while removal of the nail can improve topical drug treatment, the
ability to maintain a constant supply of the drug to the nail bed remains
problematic.
For some time, methods have been used which employ a specially formulated
antimycotic-containing medicine. Treatment of nails with a high-percentage
solution of urea and sodium metabisulfide leads to cleavage of the
disulfide linkages and hydrogen bridges of the keratin, enhancing the
penetration by the fungicide.
A number of patents and patent applications describe topical compositions,
including nail lacquers, for treating fungus of the nails. See for
example, U.S. Pat. Nos. 5,346,692; 5,391,367; 5,420,114; 5,422,366 and
5,464,610. (U.S. Pat. No. 5,464,610 also teaches a plaster composition for
treating onychomycosis.)
Thus, it would be desirable to provide improved methods and compositions
for treating fungal nail infections. Such methods and compositions should
be effective in treating the initial infection as well as inhibiting
spread of the infection to other nails and recurrence of the infection
after treatment has been completed. It would be desirable to provide
treatment methods and compositions which do not rely on the chronic
administration of anti-fungal drugs, especially systemic drugs.
U.S. Pat. No. 4,472,393 discloses 3,20-dioxo-1,4-pregnadiene-17 alpha-ol
17-aromatic heterocycle carboxylates, including mometasone furoate. U.S.
Pat. No. 4,775,529 discloses a topical formulation of mometasone furoate
in a hydro-alcoholic base. U.S. Pat. No. 4,808,610 discloses a cream
formulation including mometasone furoate. The above three patents are
hereby incorporated by reference for disclosing the active ingredient and
topical formulations including such active ingredient that are useful in
the method and compositions of the invention.
SUMMARY OF THE INVENTION
The present invention provides method and a composition for fungal nail
infections which composition comprises an effective amount of mometasone
furoate in a pharmaceutically acceptable vehicle therefore. For example,
the pharmaceutical compositions of the invention may comprise from 0.01 to
1.0%, mometasone furoate, by weight, of the total composition. Preferably,
the concentration of mometasone furoate may be within a range of from 0.02
to 0.3%, by weight, with a range of from 0.05 to 0.25% by weight, most
preferred. The pharmaceutically-acceptable vehicle may comprise a hexylene
glycol-containing cream or hydro-alcoholic lotion.
The composition of the present invention may be packaged in a number of
containers. It may be supplied in a bottle with a brush applicator similar
to a nail polish. It may also be supplied in an applicator tipped bottle.
It may also be supplied in a glass and applicator bottle.
Most preferably, the composition utilized in the treatment of onychomycosis
or nail fungus is Elocon.RTM. mometasone furoate cream 1.0% topical
composition that is sold by Schering Plough for Kenilworth, N.J. for
dermatological use.
BRIEF DESCRIPTION OF THE DRAWINGS
The advantages and features of the present invention will be better
understood by the following description when considered in conjunction
with the accompanying drawings in which:
FIG. 1 is a representation of onychomycosis of the nail of the big toe of a
human patient to be treated in accordance with the present invention;
FIG. 2 is a representation of the treatment of the onychomycosis of the big
toe shown in FIG. 1 after topical application of Elocon.RTM. for a period
of 10 weeks; and
FIG. 3 is a representation of the treatment of the onychomycosis of the big
toe shown in FIG. 1 after topical application of Elocon.RTM. for a period
of 20 weeks;
DETAILED DESCRIPTION
Fungal infections which may be treated according to the present invention
include infections from yeasts, such as Candida species, most notably
albicans; from dermatophytes, such as Trichophyton mentagrophytes,
Trichophyton rubrum, Trichophyton megninii, Trichophyton schoenleinii,
Trichophyton tonsurans, and Microsporum species; from molds, such as
Scopulariopsis cephalosporium, and Aspergillus fusarium; from
Epidermophyton species; and from Hendersonula toruloideo.
Fungal nail infections which may be treated using the methods and
compositions of the present invention are usually characterized by
tarnished white, yellowed, or blackened nails. The nails will usually pull
away from the pink nail bed along the sides or outer edges, and infections
are usually exacerbated by not, damp conditions inside the shoes or in
environments where hands or feet are continually exposed to moisture. The
fungal infections are most commonly found in the toenails and can spread
from toe to toe, foot to foot, and foot to hand. Diagnosis of the fungal
infections may be microscopic identification and/or culture of the
infected areas.
Specific infections which may be treated by the methods and compositions of
the present invention include distal subungual onychomycosis (caused by
infection with Candida trichophyton, Scopularosis, and Aspergillis);
superficial white onychomycosis (caused by Trichophyton mentagrophytes);
proximal white subungual onychomycosis (caused by Trichophyton species);
total secondary dystrophic onychomycosis (caused by yeast and
Trichophytons); and total dystrophic primary onychomycosis (caused by
Candida species).
One aspect of this invention relates to a topical lotion for use in
treating onychomycosis or nail fungus.
The present invention provides a mometasone furoate lotion formulation
exhibiting high vasoconstrictor activity. The addition of propylene glgcol
to a hydro-alcoholic lotion base exhibits significantly higher
vasoconstrictor activity than the corresponding lotion without propylene
glycol. This increase in vasoconstrictor activity appears to be unique to
propylene glycol since substitution of propylene glycol with another
glycol, such as hexylene glycol or polyethylene glycol 400, decreases the
vasoconstrictor activity of the lotion formulation.
The topical composition comprises an amount effective to treat
onychomycosis in a hydro-alcoholic base comprising:
(a) 15 to 50% by weight propylene glycol
(b) 20 to 40% by weight isopropyl alcohol
(c) 20 to 60% by weight water
(d) 0.1 to 3.0% by weight of a thickening agent
(e) sufficient buffer to adjust the pH to between 3.0 to 6.0
The lotion of the present invention comprises a therapeutically effective
amount of mometasone furoate. The therapeutically effective amount of
mometasone furoate is generally an amount of from 0.01 to 1.0% by weight
of the total composition. Ranges of 0.02 to 0.2% are particularly suitable
with a range of 0.05 to 0.1% by weight being most preferable.
This lotion composition of the present invention may contain a thickening
agent to achieve a lotion consistency. Examples of thickening agents
useful in the invention are: Carbomer 940, an acrylic acid polymer having
an approximate molecular weight of 4,000,000 and available from B. F.
Goodrich Chemical Company. Klucel.RTM., a hydroxypropyl cellulose which is
a propylene glycol ether of cellulose available from Hercules Inc.,
Methocel.RTM. A, a methyl cellulose (which is a methyl ether of cellulose)
available from Dow Chemicals; and Polyquaternium-10 which is a polymeric
quaternary ammonium salt of hydroxyethyl cellulose reacted with a
trimethyl ammonium substituted epoxide, available from Amerchol Corp.
Cosmetic preference or stability considerations will dictate selection of
the thickening agent.
The pH of the lotion composition of the present invention is generally in
the range of about 3.0 to 6.0 and preferably pH 4.0 to 5.0. Sufficient
buffer solution is added to the lotion composition to maintain the pH in
the desired range. Examples of buffers useful in the present invention are
phosphate buffers, citrate buffers, citrate-phosphate buffers.
A second aspect of the invention provides a cream formulation having
cosmetic elegance and outstanding efficacy. The cream formulation is of
special value in the topical treatment of onychomycosis or nail fungus.
The cream formulation of the present invention is a unique drug
co-solvent-in-oil emulsion for administration to warm-blooded animals,
including man, containing as the active anti-inflammatory ingredient an
effective amount of mometasone furoate. The internal phase of the emulsion
is the drug co-solvent component comprising the hexylene glycol water
mixture. In addition to the active ingredient, pharmaceutically acceptable
adjuvants, stabilizers, preservatives, whiteners, buffers and surfactants
are used in the formulation of this invention.
The cream formulation of the present invention comprises:
0.01 to 0.25% Mometasone Furoate
5 to 20% Hexylene Glycol NF
1.0 to 5.0% Water Purified USP
2.0 to 10.0% White Wax NF
4 to 12% of a lipophilic emulsifier having a HLB below 5
0.7 to 4% of a hydrophilic emulsifier having a HLB above 11
0.2 to 2.0% Titanium Dioxide USP
5 to 20% Aluminum Starch Octenylsuccinate
40 to 70% White Petrolatum USP
Sufficient acid is added to adjust the pH of the purified water to pH
2.5.+-.0.2; charged as a 10% w/v solution. Examples of acids which can be
utilized in the cream formulation are phosphoric acid, hydrochloric acid,
acetic acid, and the like. The preferred acid is phosphoric acid.
In a preferred aspect of the present invention, the formulation comprises:
0.05 to 0.15% Mometasone Furoate
9 to 15% Hexylene Glycol NF
2 to 4% Water Purified USP
4 to 6% White Wax NF
6 to 10% of a lipophilic emulsifier having a HLB below 5
1.2 to 2.5% of a hydrophilic emulsifier having a HLB above 11
0.75 to 1.25% Titanium Dioxide USP
8 to 12% Aluminum Starch Octenylsuccinate
50 to 60% White Petrolatum USP
This cream formulation results in an elegant stable, water-washable cream
with excellent anti-inflammatory activity. This cream is also
self-preserving.
The preferred lipophilic emulsifier is propylene glycol stearate. Other
acceptable lipophilic emulsifiers for use in the creams include ethylene
glycol monolaurate, ethylene glycol monostearates, propylene glycol
monolaurate and glyceryl monoricinolate.
The preferred hydrophilic emulsifier is Ceteareth-20, i.e., polyethylene
glycol ether of cetearyl alcohol that conforms generally to the formulas
R(OCH.sub.2 CH.sub.2).sub.n OH wherein R represents a blend of cetyl and
stearyl radicals and n has an average value of 30. Other acceptable
hydrophilic emulsifiers for use in the creams include polyethylene glycol
monolaurate, polyethylene glycol distearate, P.O.E. cetyl alcohol, P.O.E.
sorbitan monostearate and P.O.E. sorbitan monoleate.
Most preferably, the formulation described above as a preferred aspect of
the invention comprises:
0.1% Mometasone Furoate
9 to 15% Hexylene Glycol NF
2 to 4% Water Purified NF
4 to 6% White Wax NF
6 to 10% propylene glycol stearate
1.2 to 2.5% Ceteareth-20
0.75 to 1.25% Aluminum Starch Octenylsuccinate
50 to 60% White Petrolatum USP
This most preferred formulation may also comprise stearyl alcohol and
titanium dioxide.
The HLB is defined by Griffin, W. C., J. Soc., Cosmetic Chemist, 1,311
›1949! and 5,249 ›1949!. The HLB reflects the balance between hydrophilic
and lipophilic strength of the emulsifiers. The higher HLB, indicates a
stronger hydrophilic tendency of the emulsification system.
Treatment with the compositions of this invention is usually accomplished
by applying it to completely cover the affected area. The usual frequency
of application is once daily, although adequate maintenance therapy for
some patients may be achieved with less frequent application.
The compositions of the present invention are manufactured in a
conventional manner by thoroughly mixing the ingredients at ambient or
elevated temperatures in order to achieve solubility of ingredients where
appropriate. Preferably, in the cream formulation the mometasone furoate,
dissolved in a portion of the hexylene glycol/water mixture is added to
the oil phase. The ingredients are thoroughly mixed to that the product is
homogeneous. Processing equipment suitable for preparing the cream are
known in the art and include colloid mills, homogenizers, roller mills,
propeller mixers and the like.
All percentages are by weight. The definitions of components whose chemical
composition is not immediately clear form the name used, such as
"Ceteareth-20" and "Promulgen-G", may be found in the CTFA Cosmetic
Ingredients Dictionary, 3rd Edition, published by Cosmetic Toiletry and
Fragrance Association, Inc., Washington, D.C.
The following formulation examples illustrate the compositions of the
present invention. It will be apparent to those skilled in the art that
many modifications thereof may be practical without departing from the
purpose and intent of this disclosure.
EXAMPLE 1
A 0.1% mometasone furoate lotion formulation in accordance with the present
invention having the following composition.
______________________________________
Ingredients mg/g
______________________________________
Mometasone furoate 1.0
Alcohol Isopropyl USP 400.0
Propylene Glycol USP 300.0
Hydroxypropylcellulose
1.5
(Klucel HF)
Sodium Phosphate Monobasic
2.0
Monohydrate R
Phosphoric Acid NF (Used to
adjust the pH to 4.5 .+-. 0.1)
Water Purified USP q.s. to make 1 g
______________________________________
EXAMPLE 2
An anti-inflammatory cream is prepared from the following ingredients:
______________________________________
Ingredients Quantity, mg/g
______________________________________
Mometasone Furoate 1.0
Hexylene Glycol NF 120
Water Purified USP 30
White Wax NF 50
Propylene Glycol Stearate
80
Stearyl Alcohol and Ceteareth-20
70
(Promulgen-G)
Titanium Dioxide USP 10
Aluminum Starch Octenylsuccinate
100
Phosphoric Acid NF (To adjust the Ph
of the purified water to Ph 2.5 .+-. 2;
charged as a 10% w/v solution)
White Petrolatum USP 539
______________________________________
The cream formulation is prepared in a procedure including the following
steps:
1. In a suitable vessel charge the white petrolatum, white wax, propylene
glycol stearate and Promulgen-G. Melt and heat to 70.degree. C. with
agitation until a homogenous melted mixture is obtained.
2. In a separate vessel, prepare a 10% w/v phosphoric acid solution.
3. Charge the purified water to a suitable vessel and adjust the Ph of the
water to about 2.5 with 10% phosphoric acid solution.
4. Charge the hexylene glycol to the acidified water and adjust the Ph to
4.0 by addition of the 10% phosphoric acid solution, only if necessary.
5. Dissolve the mometasone furoate in approximately 90% of the hexylene
glycol/water at 60.degree.-65.degree. C. Heat the solution to 70.degree.
C. and charge to the mixture prepared in Step 1. Mix to achieve adequate
emulsification at 70.degree. C.
6. Rinse containers used for the active solution with the remaining 10%
hexylene glycol/water and add rinse to the emulsions prepared in Step 5.
7. Charge the titanium dioxide and aluminum starch octenylsuccinate in
small portions to Step 5 at 70.degree. C. and mix for at least twenty
minutes.
8. Cool the batch to approximately 25.degree..degree.C. with appropriate
mixing and add to appropriate containers.
EXAMPLE 3
An anti-inflammatory cream is prepared from the following ingredients:
______________________________________
Ingredients Quantity, mg/g
______________________________________
Mometasone Furoate 0.5
Hexylene Glycol NF 60.0
Water Purified USP 15.0
White Wax NF 60.0
Propylene Glycol Stearate
70.0
Stearyl Alcohol and Ceteareth-20
60.0
(Promulgen-G)
Titanium Dioxide USP 10
Aluminum Starch Octenylsuccinate
100
Phosphoric Acid NF (To adjust the Ph
of the purified water to Ph 2.5 .+-. 0.2;
charged as a 10% w/v solution.
White Petrolatum USP 624.5
______________________________________
The procedure for preparing the cream is prepared form the following
ingredients.
EXAMPLE 4
______________________________________
Ingredients Quantity, mg/g
______________________________________
Mometasone Furoate 1.0
Hexylene Glycol NF 120.0
Water Purified USP 30.0
Microcrystalline Wax 50.0
Propylene Glycol Stearate
80.0
Stearyl Alcohol and Ceteareth-20
70.0
(Promulgen-G)
Titanium Dioxide USP 8.0
Aluminum Starch Octenylsuccinate
120.0
Hydrochloric Acid NF (To adjust
the Ph of the purified water to Ph
2.5 .+-. 0.2; charged as a 10% w/v solution.
White Petrolatum USP 521.0
______________________________________
The procedure for preparing the cream is as described in Example 2.
EXAMPLE 5
______________________________________
Ingredients Quantity, mg/g
______________________________________
Mometasone Furoate 1.0
Hexylene Glycol NF 120.0
Water Purified USP 30.0
White Wax NF 50.0
Sorbitan Trioleate 80.0
Stearyl Alcohol and Ceteareth-20
70.0
(Promulgen-G)
Titanium Dioxide USP 5.0
Aluminum Starch Octenylsuccinate
150.0
Phosphoric Acid NF (To adjust the Ph
of the purified water to Ph 2.5 .+-. 0.2;
charged as a 10% w/v solution.
White Petrolatum USP 494.0
______________________________________
EXAMPLE 6
Various patients are treated for nail fungus with any of the compositions
of Examples 1 through 5 with the following results.
Patient A: Female patient in mid-forties has onychomycosis of a fingernail.
After six weeks of treatment, she has a 2 mm wide clear (i.e. uninfected)
zone of new nail at the base of the nail. The treatment has arrested
fungal growth, and the new growth (the clear zone) is uninfected. At week
12 of treatment, the clear zone is 4 mm wide, and the patient is
continuing to use the treatment.
Patient B: Female patient in her early fifties has an onychomycotic
infection of five toenails on the same foot. After 6 weeks of treatment,
the nails of the four small toes shows dramatic clearing. The nail on the
great toe has been fully involved, and new nail appears to be growing
under the old (infected) nail plate.
Patient C: Female patient in mid-thirties had repetitive episodes of
onychomycosis of the fingernails. Treatment with any of the
above-described composition is commenced. When the treatment begins, only
one nail is infected. Only that infected nail is treated with the
above-described formulations. After four weeks of treatment, the infection
is arrested in that nail (as shown by a clear zone of new growth,
uninfected nail). Furthermore, the infection has not spread to other
nails. At ten weeks of treatment, the infected nail is virtually clear
(100% uninfected), and no other nails had become infected.
Patient D: Male patient in his mid-fifties had onychomycotic infection 10
of the big toenail 12 each foot 14, a representation of one foot 14 being
shown in FIG. 1. As shown in FIG. 1, the infection 10 extended to within
about 2 mm of the cuticle 16. For 10 weeks he applied Elocon.RTM. brand of
mometasone furoate cream 0.1% to the upper nail surface of infected toes
twice daily. After the 10 week period, a clear zone of about 6 mm
extending from the cuticle was seen, as represented in FIG. 2 to the
infected area 18. After 20 weeks, the zone extended about 10 mm from the
cuticle. The result after 20 weeks, showing that the infection was
arrested, is shown in the FIG. 3 wherein the area 20 is the clear nail
zone, extending about 10 mm from the cuticle 16. The shaded area 22 is the
previously infected zone of the toenail which, is growing away from the
cuticle 16 and will eventually be scissored from the healthy nail that
extends from the cuticle. It should be appreciated that while the
formulation, in accordance with the present invention, may not directly
"kill" the infection, it makes the nail inhospitable for fungal growth. As
growth of the nail continues, new nail growth, made inhospitable to
infection, or fungal, effectively forms a complete healthy nail
Although the foregoing invention has been described in detail for purposes
of clarity of understanding, it will be obvious that certain modifications
may be practiced within the scope of the appended claims. For example the
various 3, 20 dioxo-1, 4 pregnadien-17 alpha-ol 17 aromatic heterocyclic
carboxylates, described in U.S. Pat. No 4,472,393, i.e.
##STR1##
wherein X is a member selected from the group consisting of hydrogen and
halogen having an atomic weight less than 100;
Y is a member selected from the group consisting of (H,H) provided X is
hydrogen, oxygen, (H, betaOH, and (H, beta-halogen) provided X is chlorine
or bromine, said beta-halogen having an atomic weight of less than 100,
and being at least as electronegative as X;
Z is hydrogen, CH.sub.3, chlorine, or fluorine;
V is an acyl radical of an aromatic heterocyclic carboxylic acid selected
from the group consisting of thiophenacarboxylic acid, pyrrolecarboxylic
acid and furancarboxylic acid, and methyl and halogen-substituted
derivatives thereof;
W is a member selected from the group consisting of (H, H); (H, lower
alkyl); (H, OV.sub.1) wherein V.sub.1 is a member selected from the group
consisting of hydrogen and an acyl radical of an acid selected from the
group consisting of a hydrocarboncarboxylic acid having up to 12 carbon
atoms, benzoic acid substituted by a halogen or methoxy group, retinoic
acid, and isonicotinic acid; =CHT wherein T is a member selected from the
group consisting of hydrogen, lower alkyl, fluorine, and chlorine; G is
hydrogen, a halogen having an atomic weight less than 100, or OV.sub.2
wherein V.sub.2 is a member selected from the group consisting of
hydrogen, an acyl radical of a hydrocarbon-carboxylic acid having up to 12
carbon atoms, benzoic acid substituted by a halogen or methoxy group,
retinoic acid, isonicotinic acid, and the acid radical of phosphoric acid
and mono- and dialkali and alkaline earth metal salts thereof; and the
6-dehydro and 1,2-dihydro analogs of the foregoing.
In particular, the 17 furoyl and 17 thenoyl esters of mometasone are useful
in the method of the present invention.
Although there has been hereinabove described a method of treating fungal
infection in accordance with the present invention, for the purpose of
illustrating the manner in which the invention maybe used to advantage, it
should be appreciated that the invention is not limited thereto.
Accordingly, any and all modifications, variations, or equivalent
arrangements which may occur to those skilled in the art, should be
considered to be within the scope of the present invention as defined in
the appended claims.
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